SEX AND AGE DIFFERENCES IN IMMUNITY TO INFLUENZA (SADII) SUMMARY The NIH Office of Research on Women?s Health (ORWH) should support a Specialized Center of Research Excellence (SCORE) on sex differences in influenza immunity because despite having antivirals and vaccines, influenza remains a significant public health threat, causing approximately 100,000 hospitalizations, 30,000 deaths, and approximately $7 billion in lost productivity in the United States, alone. Sex and age are emerging as two host variables that significantly impact the pathogenesis of influenza virus infection and responses to influenza vaccines. The Sex and Age Differences in Immunity to Influenza (SADII, pronounced s?d?) SCORE will leverage the internationally recognized research, resources, and educational opportunities at Johns Hopkins University to transform women?s health and impact the development of and policy decisions about influenza vaccine programs, including universal influenza vaccines. The overarching hypothesis being tested through the SADII SCORE Research Projects is that female-biased vaccine-induced immunity to influenza viruses is age-dependent and reflects both hormonal and genetic differences between the sexes that impact immune responses (i.e., both effector and memory) to influenza vaccine antigens. SADII will bring together investigators focused on 1) seasonal influenza vaccination in an existing age and sex stratified human population; 2) animal models that can test hypotheses and mechanisms of action that are inferred from studies in human populations; and 3) the contributions of age, frailty, sex, and gender to vaccine outcomes using quantitative and qualitative statistical models. By using the combined expertise in our research groups, SADII is uniquely positioned to identify the biological basis behind sex and age differences in immune responses to influenza vaccination and disseminate those findings to the broader research, clinical, and public health communities. The overarching mission of the SADII SCORE will be achieved through the following Specific Aims: 1) To provide leadership and oversight of the SADII SCORE and collaboration with other entities at Johns Hopkins and elsewhere to develop a translational research program focused on sex and age differences in immunology and infectious diseases; 2) To systematically evaluate sex differences in vaccine-induced immune responses across the life course using translational approaches involving human studies and mechanistic animal models; and 3) To meet the career enhancement needs of diverse translational scientists studying sex differences at Johns Hopkins and beyond. We are prepared to transform women?s health, sex, and gender research into a signature initiative at Johns Hopkins and in the fields of microbiology and immunology.